TY - JOUR T1 - Leukotriene (LT)C<sub>4 </sub>aggravate bleomycin-induced pulmonary fibrosis in mice JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P3755 AU - Masamitsu Tatewaki AU - Hirokuni Hirata AU - Masafumi Arima AU - Takeshi Fukuda Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P3755.abstract N2 - Background: Synthesis of cysteinyl leukotrienes (cys-LTs) is thought to cause inflammatory disorders such as bronchial asthma and allergic rhinitis. Recent reports have suggested that LTC4 is an important regulator of pulmonary fibrosis. This study examined the effect of LTC4 in LTC4 synthase-overexpressed transgenic (Tg) mice with bleomycin-induced pulmonary fibrosis. We also focused on the function of lung-derived fibroblasts in the Tg mice.Methods: Prior to administration of bleomycin, pranlukast hydrate, a cys-LT1 receptor antagonist, was intragastrically administered to Tg mice daily from the previous day of the administration. Bleomycin was administrated by intratracheal instillation. Concentrations of IL-4, -13, and TGF-β1 in BAL fluid were measured 14 days after the administration of bleomycin. And lung tissue was examined histopathologically. In addition, lung-derived fibroblasts from Tg and wild-type (WT) mice were cultured for 7 days, and LTC4 secretion and cell viability were assessed by EIA and MTT assay, respectively. And the expression of TGF-β1 mRNA was measured by real time PCR.Results: The levels of IL-4, -13, and TGF-β1, and pulmonary fibrosis were greater in Tg than in WT mice. The reduction of LTC4 function in Tg mice could be decreased both these cytokines and pulmonary fibrosis. Furthermore, continuous LTC4 secretion from fibroblasts was higher in Tg than in WT mice, while reduction of LTC4 by pranlukast in fibroblasts from Tg, but not in those from WT mice, decreased cell viability and expression of TGF-β1 mRNA.Conclusion: These findings first suggest that overexpression of LTC4 using transgenic mice is responsible for the development of pulmonary fibrosis. ER -